CLONAL EXPANSION OF P53 MUTANT-CELLS IS ASSOCIATED WITH BRAIN-TUMOR PROGRESSION
CLONAL EXPANSION OF P53 MUTANT-CELLS IS ASSOCIATED WITH BRAIN-TUMOR PROGRESSION
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DOI：
10.1038/355846a0
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发表时间：
1992-02-27
期刊：
影响因子：
64.8
通讯作者：
VOGELSTEIN, B
中科院分区：
文献类型：
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作者：
SIDRANSKY, D;MIKKELSEN, T;VOGELSTEIN, B
肿瘤进展是癌症生物学的基本特征1。癌症并不是以其最终形式从头产生的，而是开始为小的、惰性的生长，其逐渐获得与恶性肿瘤相关的特征。例如，在大脑中，低级别肿瘤（星形细胞瘤）演变为生长更快，发育不良和侵袭性更强的高级别肿瘤（胶质母细胞瘤）2，3。为了确定脑肿瘤进展背后的遗传事件，我们分析了10对原发性脑肿瘤中的p53基因。7对由表现和复发时均为高级别的肿瘤组成（A组），3对由进展为高级别肿瘤的低级别肿瘤组成（B组）。在A组对中，四个复发肿瘤含有p53基因突变;在其中三个中，在原发肿瘤中发现了相同的突变。在B组中，进展到高级别与p53基因突变相关。低级别肿瘤中存在一个细胞亚群，该亚群含有与进展为胶质母细胞瘤的复发性肿瘤细胞中主要存在的相同的p53基因突变。因此，脑肿瘤的组织学进展与先前获得p53基因突变的细胞的克隆扩增有关，赋予它们选择性生长优势。这些实验观察结果强烈支持Nowell的肿瘤进展克隆进化模型4。
TUMOUR progression is a fundamental feature of the biology of cancer 1. Cancers do not arise de novo in their final form, but begin as small, indolent growths, which gradually acquire characteristics associated with malignancy. In the brain, for example, low-grade tumours (astrocytomas) evolve into faster growing, more dysplastic and invasive high-grade tumours (glioblastomaS) 2,3. To define the genetic events underlying brain tumour progression, we analysed the p53 gene in ten primary brain tumour pairs. Seven pairs consisted of tumours that were high grade both at presentation and recurrence (group A) and three pairs consisted of low-grade tumours that had progressed to higher grade tumours (group B). In group A pairs, four of the recurrent tumours contained a p53 gene mutation; in three of them, the same mutation was found in the primary tumour. In group B pairs, progression to high grade was associated with a p53 gene mutation. A subpopulation of cells were present in the low-grade tumours that contained the same p53 gene mutation predominant in the cells of the recurrent tumours that had progressed to glioblastoma. Thus, the histological progression of brain tumours was associated with a clonal expansion of cells that had previously acquired a mutation in the p53 gene, endowing them with a selective growth advantage. These experimental observations strongly support Nowell's clonal evolution model of tumour progression 4.